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ERC FUNDED PROJECTS

ProjectProgrammed and unprogrammed genomic rearrangements during the evolution of yeast species

Researcher (PI)Kenneth Henry Wolfe

Host Institution (HI)UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN

Call DetailsAdvanced Grant (AdG), LS2, ERC-2010-AdG_20100317

SummaryBy detailed evolutionary comparisons among multiple sequenced yeast genomes, we have identified several unusual regions where our preliminary evidence suggests that previously unknown molecular biology phenomena, involving rearrangement of genomic DNA, are occurring. I now propose to use a combination of dry-lab and wet-lab experimental approaches to characterize these regions and phenomena further. One region is a 24-kb section of chromosome XIV that appears to undergo recurrent 'flip/flop' inversion between two isomers at a fairly high rate in five species as diverse as Saccharomyces cerevisiae and Naumovia castellii, leading to a 1:1 ratio of the two isomers in each species. We hypothesize that this region is the site of a programmed DNA rearrangement analogous to mating-type switching. We have also identified two new genes related to the mating-type switching endonuclease HO, but different from it, that are potentially involved in rearrangement processes though not necessarily the inversion described above. We will determine the sites of action of these endonucleases. Separately, we have found evidence for a process of recurrent deletion of DNA from regions flanking the mating-type (MAT) locus in all yeast species that are descended from the whole-genome duplication (WGD) event, causing continual transpositions of genes from beside MAT to other locations in the genome. In related computational work, we propose to investigate an hypothesis that evolutionary loss of the MATa2 transcriptional activator may have been the cause of the WGD event.

By detailed evolutionary comparisons among multiple sequenced yeast genomes, we have identified several unusual regions where our preliminary evidence suggests that previously unknown molecular biology phenomena, involving rearrangement of genomic DNA, are occurring. I now propose to use a combination of dry-lab and wet-lab experimental approaches to characterize these regions and phenomena further. One region is a 24-kb section of chromosome XIV that appears to undergo recurrent 'flip/flop' inversion between two isomers at a fairly high rate in five species as diverse as Saccharomyces cerevisiae and Naumovia castellii, leading to a 1:1 ratio of the two isomers in each species. We hypothesize that this region is the site of a programmed DNA rearrangement analogous to mating-type switching. We have also identified two new genes related to the mating-type switching endonuclease HO, but different from it, that are potentially involved in rearrangement processes though not necessarily the inversion described above. We will determine the sites of action of these endonucleases. Separately, we have found evidence for a process of recurrent deletion of DNA from regions flanking the mating-type (MAT) locus in all yeast species that are descended from the whole-genome duplication (WGD) event, causing continual transpositions of genes from beside MAT to other locations in the genome. In related computational work, we propose to investigate an hypothesis that evolutionary loss of the MATa2 transcriptional activator may have been the cause of the WGD event.

Host Institution (HI)THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

Call DetailsAdvanced Grant (AdG), SH6, ERC-2011-ADG_20110406

SummaryThrough animal domestication humans profoundly altered their relationship with nature, controlling the breeding of their major food sources for material, social or symbolic profit. Understanding this complex process is a compelling research aim. There is a need to develop new high-resolution genetic tools to put flesh on the bones of this two-millenium long transition. These will take advantage of very recent advances: targeted next generation DNA sequencing, high throughput screening of expertly provenanced archaeological samples, and emerging knowledge of modern cattle, sheep and goat genome science plus their genetic geographies. Combining these, this proposal will develop an ancient DNA data matrix that will be unparalleled in archaeological science. These data will unlock the key genetic changes that accompany the domestic state and the breeding structures that are a consequence of human management. It will also identify the wild and proto-domestic populations that later herds emerge from. A more precise geography and timing of the key changes will enable richer contextualising inform our assessement of why these changes take place. The 10,000 year matrix for each species will function as a standard spatiotemporal reference grid on which any subsequent bone or animal artefact may be placed i.e. via genetic postcoding. Exceptional discontinuities in the matrix will highlight points of strong historical interest such as the emergence of new trade networks, migrations and periods of economic turbulence - perhaps driven by climate fluctuations or plagues. The final work objectives will focus on diachronic sample assemblages selected to have particular import for both historical events and transitions in material culture. For example, manuscript vellum samples will give a uniquely dated series that will enable correlation of genetic change with historical studies of the timing and impact of past animal plagues (e.g. in C 14th and C 18th Europe).

Through animal domestication humans profoundly altered their relationship with nature, controlling the breeding of their major food sources for material, social or symbolic profit. Understanding this complex process is a compelling research aim. There is a need to develop new high-resolution genetic tools to put flesh on the bones of this two-millenium long transition. These will take advantage of very recent advances: targeted next generation DNA sequencing, high throughput screening of expertly provenanced archaeological samples, and emerging knowledge of modern cattle, sheep and goat genome science plus their genetic geographies. Combining these, this proposal will develop an ancient DNA data matrix that will be unparalleled in archaeological science. These data will unlock the key genetic changes that accompany the domestic state and the breeding structures that are a consequence of human management. It will also identify the wild and proto-domestic populations that later herds emerge from. A more precise geography and timing of the key changes will enable richer contextualising inform our assessement of why these changes take place. The 10,000 year matrix for each species will function as a standard spatiotemporal reference grid on which any subsequent bone or animal artefact may be placed i.e. via genetic postcoding. Exceptional discontinuities in the matrix will highlight points of strong historical interest such as the emergence of new trade networks, migrations and periods of economic turbulence - perhaps driven by climate fluctuations or plagues. The final work objectives will focus on diachronic sample assemblages selected to have particular import for both historical events and transitions in material culture. For example, manuscript vellum samples will give a uniquely dated series that will enable correlation of genetic change with historical studies of the timing and impact of past animal plagues (e.g. in C 14th and C 18th Europe).

Max ERC Funding

2 499 693 €

Duration

Start date: 2012-07-01, End date: 2018-06-30

Project acronymCOGNET

ProjectCognitive Networks for Intelligent Materials and Devices

Researcher (PI)John Boland

Host Institution (HI)THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

Call DetailsAdvanced Grant (AdG), PE5, ERC-2012-ADG_20120216

Summary"COGnitive NETwork (COGNET) is a new technology platform for materials, sensor and device design that exploits unique and hitherto unrecognised properties of random nanowire (NW) networks. These networks—comprised of metallic or semiconducting NWs connected to each other via junctions with controllably random property distributions—lead to new and unexpected levels of connectivity that are inherently scale dependent, creating opportunities for entirely new kinds of self-organised materials and devices. We propose to establish the ground rules for manipulating connectivity in NW networks. By choosing appropriate NWs and incorporating junctions with the approprate properties COGNET will enable the fabrication of (i) intelligent materials, (ii) neural networks and (iii) memory devices. Sequenced voltage pulse and back-gating techniques will in turn address and manipulate specific junctions or sets of junctions to demonstrate even higher density memory and in the case of neural networks, the possibility synaptic plasticity and self-learning."

"COGnitive NETwork (COGNET) is a new technology platform for materials, sensor and device design that exploits unique and hitherto unrecognised properties of random nanowire (NW) networks. These networks—comprised of metallic or semiconducting NWs connected to each other via junctions with controllably random property distributions—lead to new and unexpected levels of connectivity that are inherently scale dependent, creating opportunities for entirely new kinds of self-organised materials and devices. We propose to establish the ground rules for manipulating connectivity in NW networks. By choosing appropriate NWs and incorporating junctions with the approprate properties COGNET will enable the fabrication of (i) intelligent materials, (ii) neural networks and (iii) memory devices. Sequenced voltage pulse and back-gating techniques will in turn address and manipulate specific junctions or sets of junctions to demonstrate even higher density memory and in the case of neural networks, the possibility synaptic plasticity and self-learning."

Max ERC Funding

2 497 125 €

Duration

Start date: 2013-06-01, End date: 2018-05-31

Project acronymDEVHEALTH

ProjectUNDERSTANDING HEALTH ACROSS THE LIFECOURSE:
AN INTEGRATED DEVELOPMENTAL APPROACH

Researcher (PI)James Joseph Heckman

Host Institution (HI)UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN

Call DetailsAdvanced Grant (AdG), SH1, ERC-2010-AdG_20100407

SummaryThis proposal seeks support for a research group led by James Heckman of the Geary Institute at University College Dublin to produce an integrated developmental approach to health that studies the origins and the evolution of health inequalities over the lifecourse and across generations, and the role played by cognition, personality, genes, and environments. Major experimental and nonexperimental international datasets will be analyzed. A practical guide to implementing related policy will be produced. We will build a science of human development that draws on, extends, and unites research on the biology and epidemiology of health disparities with medical economics and the economics of skill formation. The goal is to develop an integrated framework to jointly model the economic, social and biological mechanisms that produce the evolution and the intergenerational transmission of health and of the capabilities that foster health. The following tasks will be undertaken: (1) We will quantify the importance of early-life conditions in explaining the existence of health disparities across the lifecourse. (2) We will understand how health inequalities are transmitted across generations. (3) We will assess the health benefits from early childhood interventions. (4) We will examine the role of genes and environments in the aetiology and evolution of disease. (5) We will analyze how health inequalities emerge and evolve across the lifecourse. (6) We will give biological foundations to both our models and the health measures we will use. The proposed research will investigate causal channels for promoting health. It will compare the relative effectiveness of interventions at various stages of the life cycle and the benefits and costs of later remediation if early adversity is not adequately eliminated. It will guide the design of current and prospective experimental and longitudinal studies and policy formulation, and will train young scholars in frontier methods of research

This proposal seeks support for a research group led by James Heckman of the Geary Institute at University College Dublin to produce an integrated developmental approach to health that studies the origins and the evolution of health inequalities over the lifecourse and across generations, and the role played by cognition, personality, genes, and environments. Major experimental and nonexperimental international datasets will be analyzed. A practical guide to implementing related policy will be produced. We will build a science of human development that draws on, extends, and unites research on the biology and epidemiology of health disparities with medical economics and the economics of skill formation. The goal is to develop an integrated framework to jointly model the economic, social and biological mechanisms that produce the evolution and the intergenerational transmission of health and of the capabilities that foster health. The following tasks will be undertaken: (1) We will quantify the importance of early-life conditions in explaining the existence of health disparities across the lifecourse. (2) We will understand how health inequalities are transmitted across generations. (3) We will assess the health benefits from early childhood interventions. (4) We will examine the role of genes and environments in the aetiology and evolution of disease. (5) We will analyze how health inequalities emerge and evolve across the lifecourse. (6) We will give biological foundations to both our models and the health measures we will use. The proposed research will investigate causal channels for promoting health. It will compare the relative effectiveness of interventions at various stages of the life cycle and the benefits and costs of later remediation if early adversity is not adequately eliminated. It will guide the design of current and prospective experimental and longitudinal studies and policy formulation, and will train young scholars in frontier methods of research

Max ERC Funding

2 505 222 €

Duration

Start date: 2011-05-01, End date: 2016-04-30

Project acronymEASY

ProjectEjection Accretion Structures in YSOs (EASY)

Researcher (PI)Thomas RAY

Host Institution (HI)DUBLIN INSTITUTE FOR ADVANCED STUDIES

Call DetailsAdvanced Grant (AdG), PE9, ERC-2016-ADG

SummaryFor a number of reasons, in particular their proximity and the abundant range of diagnostics to determine their characteristics, outflows from young stellar objects (YSOs) offer us the best opportunity of discovering how astrophysical jets are generated and the nature of the link between outflows and their accretion disks. Models predict that the jet is initially launched from within 0.1 to a few au of the star and focused on scales at most ten times larger. Thus, even for the nearest star formation region, we need high spatial resolution to image the “central engine” and test current models.
With these ideas in mind, and the availability of a whole new set of observational and computational resources, it is proposed to investigate the origin of YSO jets, and the jet/accretion zone link, using a number of highly novel approaches to test magneto-hydrodynamic (MHD) models including:
(a) Near-infrared interferometry to determine the spatial distribution and kinematics of the outflow as it is launched as a way of discriminating between competing models.
(b) A multi-epoch study of the strength and configuration of the magnetic field of the parent star to see whether model values and geometries agree with observations and the nature of its variability.
(c) Examining, through high spatial resolution radio observations, how the ionized component of these jets are collimated very close to the source and how shocks in the flow can give rise to low energy cosmic rays.
(d) Use the James Webb Space Telescope (JWST) and, in particular, the Mid-Infrared Instrument (MIRI) and Near-Infrared Spectrograph (NIRSpec) to investigate with high spatial resolution atomic jets from protostars that are still acquiring most of their mass. In addition, we will study how accretion is affected by metallicity by studying young solar-like stars in the low metallicity Magellanic Clouds.
In all cases the required observational campaigns have been approved.

For a number of reasons, in particular their proximity and the abundant range of diagnostics to determine their characteristics, outflows from young stellar objects (YSOs) offer us the best opportunity of discovering how astrophysical jets are generated and the nature of the link between outflows and their accretion disks. Models predict that the jet is initially launched from within 0.1 to a few au of the star and focused on scales at most ten times larger. Thus, even for the nearest star formation region, we need high spatial resolution to image the “central engine” and test current models.
With these ideas in mind, and the availability of a whole new set of observational and computational resources, it is proposed to investigate the origin of YSO jets, and the jet/accretion zone link, using a number of highly novel approaches to test magneto-hydrodynamic (MHD) models including:
(a) Near-infrared interferometry to determine the spatial distribution and kinematics of the outflow as it is launched as a way of discriminating between competing models.
(b) A multi-epoch study of the strength and configuration of the magnetic field of the parent star to see whether model values and geometries agree with observations and the nature of its variability.
(c) Examining, through high spatial resolution radio observations, how the ionized component of these jets are collimated very close to the source and how shocks in the flow can give rise to low energy cosmic rays.
(d) Use the James Webb Space Telescope (JWST) and, in particular, the Mid-Infrared Instrument (MIRI) and Near-Infrared Spectrograph (NIRSpec) to investigate with high spatial resolution atomic jets from protostars that are still acquiring most of their mass. In addition, we will study how accretion is affected by metallicity by studying young solar-like stars in the low metallicity Magellanic Clouds.
In all cases the required observational campaigns have been approved.

Max ERC Funding

1 853 090 €

Duration

Start date: 2017-10-01, End date: 2022-09-30

Project acronymEIRENE

ProjectPost-war trasistions in gendered perspective: the case of the North-Eastern Adricatic Region

Researcher (PI)Marta VERGINELLA

Host Institution (HI)UNIVERZA V LJUBLJANI

Call DetailsAdvanced Grant (AdG), SH6, ERC-2016-ADG

SummaryThe EIRENE project’s purpose is to think afresh 20th-century post-war transitions by taking into account a gendered perspective. Namely, the historiographic consideration of gender thoroughly alters the understanding of social dynamics in multi-ethnic areas during the post-war transitions. They will be observed in the North-Eastern Adriatic region, an overlooked European space, marked by border redefinitions, changes of political systems, and high interethnic conflict intensity, but also by genuine cooperation among ethnic groups. The region has all the qualities of a “laboratory environment” for the study of gender positions and interrelations after World Wars I and II and after the Yugoslav wars in the 1990s. The project will differ substantially from previous attempts to analyse post-war transitions in these aspects: a) longitudinal approach, comparing three post-war periods in order to detect their specifics and (dis)continuities; b) transnational approach, by overcoming nation-centric frameworks of analysis; c) by combining conceptual political and social sciences with historiography; and finally, d) by examining post-war transitions through the prism of gender. Focusing on four research-fields (politics, political violence, work, family), the project will validate innovative analytical concepts of the “inclusion-exclusion paradox” of women in post-war transitions, and women as “cross-boundary mediators”. Within the category of gender, focal attention will be given to women as they are often invisible in historical accounts and remain neglected in historicizing. By aggregating empirical sources, the project will approach the proposed subject matter by investigating the processes of identification across the lines of ethnic origin, class, generations, marital status, profession/occupation, language of use, migratory processes, etc. The project’s added value is its novel conceptual applicability to other comparable geopolitical areas.

The EIRENE project’s purpose is to think afresh 20th-century post-war transitions by taking into account a gendered perspective. Namely, the historiographic consideration of gender thoroughly alters the understanding of social dynamics in multi-ethnic areas during the post-war transitions. They will be observed in the North-Eastern Adriatic region, an overlooked European space, marked by border redefinitions, changes of political systems, and high interethnic conflict intensity, but also by genuine cooperation among ethnic groups. The region has all the qualities of a “laboratory environment” for the study of gender positions and interrelations after World Wars I and II and after the Yugoslav wars in the 1990s. The project will differ substantially from previous attempts to analyse post-war transitions in these aspects: a) longitudinal approach, comparing three post-war periods in order to detect their specifics and (dis)continuities; b) transnational approach, by overcoming nation-centric frameworks of analysis; c) by combining conceptual political and social sciences with historiography; and finally, d) by examining post-war transitions through the prism of gender. Focusing on four research-fields (politics, political violence, work, family), the project will validate innovative analytical concepts of the “inclusion-exclusion paradox” of women in post-war transitions, and women as “cross-boundary mediators”. Within the category of gender, focal attention will be given to women as they are often invisible in historical accounts and remain neglected in historicizing. By aggregating empirical sources, the project will approach the proposed subject matter by investigating the processes of identification across the lines of ethnic origin, class, generations, marital status, profession/occupation, language of use, migratory processes, etc. The project’s added value is its novel conceptual applicability to other comparable geopolitical areas.

Max ERC Funding

2 266 067 €

Duration

Start date: 2017-12-01, End date: 2022-11-30

Project acronymFUTURE-PRINT

ProjectTuneable 2D Nanosheet Networks for Printed Electronics

Researcher (PI)Jonathan Nesbitt COLEMAN

Host Institution (HI)THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

Call DetailsAdvanced Grant (AdG), PE5, ERC-2015-AdG

SummaryIn the future, even the most mundane objects will contain electronic circuitry allowing them to gather, process, display and transmit information. The resulting vast network, often called the Internet of Things, will revolutionise society. To realise this will require the ability to produce electronic circuitry extremely cheaply, often on unconventional substrates. This will be achieved through printed electronics, by the assembly of devices from solution (i.e. ink) using methods adapted from printing technology. However, while printed electronics has been advancing rapidly, the development of new, nano-materials-based inks is required for this area to meet its true potential.
We believe recent developments in liquid exfoliation of 2D nanosheets have given us the ideal family of materials to revolutionise electronic ink production. Liquid exfoliation can transform layered crystals into suspensions of nanosheets in very large quantities. In this way we can produce liquid-dispersed nanosheets of a wide range of types including conducting (e.g. graphene, MXenes, TiB2 etc), semiconducting (e.g. MoS2, WSe2, GaS, Black phosphorous etc), insulating (e.g. BN, talc) or electrochemically active (e.g. MoO3, Ni(OH)2, MnO2 etc). These nanosheets can be deposited from liquid to form porous networks of defined electronic type. While these networks have huge applications potential, a large amount of work must be done to translate them into working printed devices.
In this project, we will develop methods to transform large volume suspensions of exfoliated nanosheets into bespoke 2D inks with properties engineered for a range of specific printed device applications. We will learn to use this 2D ink to print patterned or large area 2D nanosheet networks with controlled structure, allowing us to tune the electrical properties of the network during printing. We will combine networks of different nanosheet types into complex heterostructures. This will allow us to print all device components (electrodes, active layers, dielectrics, energy storage layers) from one contiguous, multi-component network. In this way we will produce 2D network transistors, solar cells, displays and energy storage systems. FUTURE-PRINT will revolutionise electronic inks and will offer a new path forward for printed electronics.

In the future, even the most mundane objects will contain electronic circuitry allowing them to gather, process, display and transmit information. The resulting vast network, often called the Internet of Things, will revolutionise society. To realise this will require the ability to produce electronic circuitry extremely cheaply, often on unconventional substrates. This will be achieved through printed electronics, by the assembly of devices from solution (i.e. ink) using methods adapted from printing technology. However, while printed electronics has been advancing rapidly, the development of new, nano-materials-based inks is required for this area to meet its true potential.
We believe recent developments in liquid exfoliation of 2D nanosheets have given us the ideal family of materials to revolutionise electronic ink production. Liquid exfoliation can transform layered crystals into suspensions of nanosheets in very large quantities. In this way we can produce liquid-dispersed nanosheets of a wide range of types including conducting (e.g. graphene, MXenes, TiB2 etc), semiconducting (e.g. MoS2, WSe2, GaS, Black phosphorous etc), insulating (e.g. BN, talc) or electrochemically active (e.g. MoO3, Ni(OH)2, MnO2 etc). These nanosheets can be deposited from liquid to form porous networks of defined electronic type. While these networks have huge applications potential, a large amount of work must be done to translate them into working printed devices.
In this project, we will develop methods to transform large volume suspensions of exfoliated nanosheets into bespoke 2D inks with properties engineered for a range of specific printed device applications. We will learn to use this 2D ink to print patterned or large area 2D nanosheet networks with controlled structure, allowing us to tune the electrical properties of the network during printing. We will combine networks of different nanosheet types into complex heterostructures. This will allow us to print all device components (electrodes, active layers, dielectrics, energy storage layers) from one contiguous, multi-component network. In this way we will produce 2D network transistors, solar cells, displays and energy storage systems. FUTURE-PRINT will revolutionise electronic inks and will offer a new path forward for printed electronics.

Max ERC Funding

2 213 317 €

Duration

Start date: 2016-11-01, End date: 2021-10-31

Project acronymIntRanSt

ProjectIntegrable Random Structures

Researcher (PI)Neil O'Connell

Host Institution (HI)UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN

Call DetailsAdvanced Grant (AdG), PE1, ERC-2014-ADG

SummaryThe last few years have seen significant advances in the discovery and development of integrable models in probability, especially in the context of random polymers and the Kardar-Parisi-Zhang (KPZ) equation. Among these are the semi-discrete (O'Connell-Yor) and log-gamma (Seppalainen) random polymer models. Both of these models can be understood via a remarkable connection between the geometric RSK correspondence (a geometric lifting, or de-tropicalization, of the classical RSK correspondence) and the quantum Toda lattice, the eigenfunctions of which are known as Whittaker functions. This connection was discovered by the PI and further developed in collaboration with Corwin, Seppalainen and Zygouras. In particular, we have recently introduced a powerful combinatorial framework which underpins this connection. I have also explored this connection from an integrable systems point of view, revealing a very precise relation between classical, quantum and stochastic integrability in the context of the Toda lattice and some other integrable systems. The main objectives of this proposal are (1) to further develop the combinatorial framework in several directions which, in particular, will yield a wider family of integrable models, (2) to clarify and extend the relation between classical, quantum and stochastic integrability to a wider setting, and (3) to study thermodynamic and KPZ scaling limits of Whittaker functions (and associated measures) and their applications. The proposed research, which lies at the interface of probability, integrable systems, random matrices, statistical physics, automorphic forms, algebraic combinatorics and representation theory, will make novel contributions in all of these areas.

The last few years have seen significant advances in the discovery and development of integrable models in probability, especially in the context of random polymers and the Kardar-Parisi-Zhang (KPZ) equation. Among these are the semi-discrete (O'Connell-Yor) and log-gamma (Seppalainen) random polymer models. Both of these models can be understood via a remarkable connection between the geometric RSK correspondence (a geometric lifting, or de-tropicalization, of the classical RSK correspondence) and the quantum Toda lattice, the eigenfunctions of which are known as Whittaker functions. This connection was discovered by the PI and further developed in collaboration with Corwin, Seppalainen and Zygouras. In particular, we have recently introduced a powerful combinatorial framework which underpins this connection. I have also explored this connection from an integrable systems point of view, revealing a very precise relation between classical, quantum and stochastic integrability in the context of the Toda lattice and some other integrable systems. The main objectives of this proposal are (1) to further develop the combinatorial framework in several directions which, in particular, will yield a wider family of integrable models, (2) to clarify and extend the relation between classical, quantum and stochastic integrability to a wider setting, and (3) to study thermodynamic and KPZ scaling limits of Whittaker functions (and associated measures) and their applications. The proposed research, which lies at the interface of probability, integrable systems, random matrices, statistical physics, automorphic forms, algebraic combinatorics and representation theory, will make novel contributions in all of these areas.

Max ERC Funding

1 579 299 €

Duration

Start date: 2015-10-01, End date: 2020-09-30

Project acronymMICROINNATE

ProjectAn exploration into the role of microRNAs in innate immune signaling

Researcher (PI)Luke O'neill

Host Institution (HI)THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

Call DetailsAdvanced Grant (AdG), LS6, ERC-2010-AdG_20100317

SummaryMicroRNAs (miRNAs) are important regulators of both innate and adaptive immunity. This is very much a frontier area since little is known about miRNA function in vivo, and there is still much discovery to be done. Their emerging functions indicate that they are as potent as cytokines in immunoregulation.
We have found that Toll-like receptor (TLR) signaling is potently modulated by 2 particular miRNAs, miR-21 and miR-107. The programme will have 4 aspects which will build on this initial observation.
1. Extension of our observations on miR-21 and TLR signaling. We found that the translational repressor PDCD4 is a key target. We will study miR-21-deficient mice, construct a mouse model where the miR-21 seed sequence in the 3'UTR of PDCD4 is altered, and target miR-21 in vivo using antagomirs. We will also determine the mRNAs regulated by PDCD4 and examine the role of mTOR in PDCD4 control since PDCD4 is a possible substrate.
2. Examination of the role of miR-107 in TLR signaling. TLRs dramatically decrease it¿s expression. We have found that miR-107 has an inhibitory role in TNF secretion via the targeting of CDK6. Activation of PPAR-alpha increases expression of miR107, which could be part of the anti-inflammatory effect of PPAR-alpha ligands. We will explore miR-107-deficient mice and in vitro models of miR-107 function.
3. Exploring the targeting of miR-155 by IL10, which we have recently found. The miR-155 target SHIP1 may be important in this system. We will analyze this process in detail and determine other targets for miR-155 in IL10 action.
4. Perform a screen for novel regulators of the aforementioned miRNAs and screen for miRNAs as regulators of other innate immune pathways, including Nalp3 and RIG-I, about which little is known. These experiments will yield new insights and components
The focus is the complex role miRNAs are playing in innate immunity and inflammation.

MicroRNAs (miRNAs) are important regulators of both innate and adaptive immunity. This is very much a frontier area since little is known about miRNA function in vivo, and there is still much discovery to be done. Their emerging functions indicate that they are as potent as cytokines in immunoregulation.
We have found that Toll-like receptor (TLR) signaling is potently modulated by 2 particular miRNAs, miR-21 and miR-107. The programme will have 4 aspects which will build on this initial observation.
1. Extension of our observations on miR-21 and TLR signaling. We found that the translational repressor PDCD4 is a key target. We will study miR-21-deficient mice, construct a mouse model where the miR-21 seed sequence in the 3'UTR of PDCD4 is altered, and target miR-21 in vivo using antagomirs. We will also determine the mRNAs regulated by PDCD4 and examine the role of mTOR in PDCD4 control since PDCD4 is a possible substrate.
2. Examination of the role of miR-107 in TLR signaling. TLRs dramatically decrease it¿s expression. We have found that miR-107 has an inhibitory role in TNF secretion via the targeting of CDK6. Activation of PPAR-alpha increases expression of miR107, which could be part of the anti-inflammatory effect of PPAR-alpha ligands. We will explore miR-107-deficient mice and in vitro models of miR-107 function.
3. Exploring the targeting of miR-155 by IL10, which we have recently found. The miR-155 target SHIP1 may be important in this system. We will analyze this process in detail and determine other targets for miR-155 in IL10 action.
4. Perform a screen for novel regulators of the aforementioned miRNAs and screen for miRNAs as regulators of other innate immune pathways, including Nalp3 and RIG-I, about which little is known. These experiments will yield new insights and components
The focus is the complex role miRNAs are playing in innate immunity and inflammation.

Max ERC Funding

2 480 587 €

Duration

Start date: 2011-06-01, End date: 2016-05-31

Project acronymMULTIWAVE

ProjectMultidisciplinary Studies of Extreme and Rogue Wave Phenomena

Researcher (PI)Frederic Dias

Host Institution (HI)UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN

Call DetailsAdvanced Grant (AdG), PE2, ERC-2011-ADG_20110209

SummaryMULTIWAVE is an interdisciplinary project at the frontiers of mathematics, physics and engineering which will explore important open questions in nonlinear wave propagation and the emergence of extreme events. The work necessitates a Co-Investigator approach in order to carry out coordinated analytical, numerical and experimental studies of the nonlinear effects that form the subject of the proposal. The project builds on recent international developments in the field of nonlinear waves led by the co-investigators that have shown how analogies between optical systems and the deep ocean provide new insights into the generation of the infamous hydrodynamic rogue waves on the ocean. These results, which have led to the first experimental confirmation in 2010 of analytic predictions of hydrodynamics that have remained untested for 25 years, have now opened up the possibility for an optical system to directly study the dynamics and statistics of extreme nonlinear wave shaping. This is a tremendous advance comparable to the introduction of optical systems to study chaos in the 1970s, and the co-investigators aim to be at the forefront of this research effort. Core theoretical elements in the project will uncover the fundamental mechanisms underlying the emergence of large scale coherent structures from a turbulent environment, and resolve basic questions of energy transport in the presence of nonlinearity. These analytical studies will be complemented by numerical simulations and laboratory experiments in optical systems. Specifically, recent advances in optical technology will enable the benchtop development of an “optical wave tank” that will accurately simulate multiple propagation scenarios in hydrodynamics and ocean systems. Emphasis will be placed on extreme rogue wave events which are difficult or even impossible to study quantitatively in their natural oceanic environment.

MULTIWAVE is an interdisciplinary project at the frontiers of mathematics, physics and engineering which will explore important open questions in nonlinear wave propagation and the emergence of extreme events. The work necessitates a Co-Investigator approach in order to carry out coordinated analytical, numerical and experimental studies of the nonlinear effects that form the subject of the proposal. The project builds on recent international developments in the field of nonlinear waves led by the co-investigators that have shown how analogies between optical systems and the deep ocean provide new insights into the generation of the infamous hydrodynamic rogue waves on the ocean. These results, which have led to the first experimental confirmation in 2010 of analytic predictions of hydrodynamics that have remained untested for 25 years, have now opened up the possibility for an optical system to directly study the dynamics and statistics of extreme nonlinear wave shaping. This is a tremendous advance comparable to the introduction of optical systems to study chaos in the 1970s, and the co-investigators aim to be at the forefront of this research effort. Core theoretical elements in the project will uncover the fundamental mechanisms underlying the emergence of large scale coherent structures from a turbulent environment, and resolve basic questions of energy transport in the presence of nonlinearity. These analytical studies will be complemented by numerical simulations and laboratory experiments in optical systems. Specifically, recent advances in optical technology will enable the benchtop development of an “optical wave tank” that will accurately simulate multiple propagation scenarios in hydrodynamics and ocean systems. Emphasis will be placed on extreme rogue wave events which are difficult or even impossible to study quantitatively in their natural oceanic environment.